title: Rapamycin attenuates the severity of murine adriamycin nephropathy.
abstract: BACKGROUND
  Rapamycin is an immunosuppressive drug with potent antifibrotic activity. We evaluated the effect of rapamycin on murine adriamycin nephropathy, a model of progressive glomerulosclerosis and tubulointerstitial fibrosis.
  
  
  METHODS
  Adriamycin nephropathy was induced in Balb/c mice by a single intravenous injection of adriamycin. The mice were treated orally with either saline or rapamycin, beginning at the time of adriamycin injection or rapamycin starting 1 week after adriamycin injection. The mice were sacrificed 6 weeks after adriamycin injection.
  
  
  RESULTS
  Saline-treated mice developed massive proteinuria and impaired renal function. Kidney sections from saline-treated mice showed marked focal segmental glomerulosclerosis, tubular dilation with protein cast deposition, interstitial fibrosis, and numerous infiltrating macrophages and T lymphocytes. The intrarenal expression of Collagen I and RANTES was also increased. In contrast, both groups of rapamycin-treated mice had markedly reduced proteinuria and preserved renal function, with only mild histological abnormalities. The intrarenal expression of Collagen I and RANTES was reduced, concomitant with a significant reduction in interstitial inflammatory cell infiltration.
  
  
  CONCLUSIONS
  Rapamycin is effective in attenuating the glomerular and tubulointerstitial abnormalities in adriamycin nephropathy. The beneficial effects of rapamycin are mediated, at least in part, through reduced RANTES expression and inflammatory cell infiltration.
authors.affiliation: Dr. Lee Iu Cheung Memorial Renal Research Center, Tung Wah Hospital, Hong Kong SAR, China.
authors.forename: Sing Leung
authors.initials: SL
authors.lastname: Lui
authors.forename: Ryan
authors.initials: R
authors.lastname: Tsang
authors.forename: Kwok Wah
authors.initials: KW
authors.lastname: Chan
authors.forename: Florence
authors.initials: F
authors.lastname: Zhang
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Susan
authors.initials: S
authors.lastname: Yung
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
mesh_terms: D000419:Albuminuria / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001835:Body Weight; D018946:Chemokine CCL5 / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012720:Severity of Illness Index; D020123:Sirolimus / Q000494:pharmacology*; D015996:Survival Rate
chemical_list: D000903:Antibiotics, Antineoplastic; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D024042:Collagen Type I; D007166:Immunosuppressive Agents; D004317:Doxorubicin; D020123:Sirolimus